To provide much needed information on the immune response of pneumococcal vaccine (PV) in older persons, we have designed a double-blind alternate-vaccine cohort study. We will enroll approximately 120 patients and residents, ages 50-79 and 80 plus, in nursing homes and approximately 120, age and sex matched, persons in apartments. We will compare their antibody responses following PV with those of 30 young adults. We will administer tetanus-diphtheria toxoid to a 20 percent sample of roommates to evaluate confounding effects of carriage, inapparent infection, etc. Measurements will include: type-specific antibody (total) to 12 of the 14 pneumococcal polysaccharides in the PV vaccine by RIA; immunoglobulin classes (IgG, IgA and IgM) distribution of antibody to types 3, 6 and 9 by ELISA and antibody to phosphorylcholine (PC), a major antigenic determinant of C-polysaccharide, by ELISA. Tetanus anti-toxin antibody levels will be measured by ELISA as a non-carbohydrate protein in vaccine control. Serum immunoglobulin levels will be determined to exclude a latent immunodeficiency. We will determine the amount, class and duration of type-specific antibody and the amount and duration of antibody to PC by comparing the pre-vaccination antibody levels (geometric means [GM]) versus the 1-month post-PV antibody levels (number [percent]) with 2-fold increase in GM antibody titer and number (percent) with 300 ng of antibody nitrogen/ml) versus the antibody levels at 6, 12 and 24-months post-PV. We will compare for age and sex within groups using the individual as his own control and compare between groups. We will identify individuals who respond poorly to PV by evaluating the predicted value of serum immunoglobulin and IgG subclass levels. Because nontype-specific antibody is more likely to occur following natural infection, we will also measure antibody to PC in post-pneumococcal pneumonia sera. The long-range objectives are to develop an effective strategy to prevent pneumococcal pneumonia in the elderly. If the current PV does not induce persistent protective antibody levels, then we will study new vaccines with the polysaccharides covalently coupled to protein carriers. If a response to PC occurs after pneumococcal pneumonia, and is correlated with protective type-specific antibody levels, a vaccine to induce antibody to this antigen would be an attractive alternative to a multi-valent capsular vaccine.